“GDF15 is a stress-induced hormone that may mediate an aversive dietary response”
Recent research has shown that GDF15 expression is regulated by the integrated stress response. Rather than being produced in response to acute dietary changes, the production of GD15 is triggered by ongoing nutritional stress, exemplified by chronic high-fat or acute lysine-deficient diets. In addition, GDF15 administration was shown to trigger conditioned taste aversion in mice.
GDF15 (growth differentiation factor 15) is known to be produced in response to various forms of stress. It can be expressed in most types of cell and has recently been adopted in clinical practice as a diagnostic biomarker in mitochondrial disease and as a prognostic marker in conditions such as heart failure and cancer.
Since mice lacking GDF15 or the receptor on which it acts (GFRAL) have been found to develop diet-induced obesity, and those overexpressing GDF15 lost weight dramatically, it became apparent that GDF15 may also play a physiological role in energy balance and nutrient control.
Serum levels of GD15 have been shown to increase with age, smoking, intense exercise, cancer, and a range of other disease states, but the nutritional states that trigger its production had not been fully elucidated.
The latest research investigated how changes in nutritional state affected the expression of GDF15 in a series of mouse and human studies. The effects on body weight and circulating GD15 concentration were measured after following one of several different dietary regimes, eg, calorie deprivation, short-term high-fat over-feeding. In addition, elements of the cellular integrated stress response (ISR) that are involved in the regulation of GDF15 expression were studied in mice.
In the mouse studies, body composition was determined every 4 weeks by time-domain nuclear magnetic resonance (TD-NMR) using a Bruker Minispec LF series NMR spectrometer.
Unlike the classic intestinal hormones and leptin, which are produced in response to satiety, neither calorie surpluses nor calorie deficits of moderate duration had significant effect on the circulating levels of GDF15. In contrast, mice who received a diet high in fat or with an amino acid imbalance for a prolonged period were found to have increased levels of GD15.
Such diets were also shown to activate the ISR in certain tissues. In addition, acute administration of GDF15 elicited an aversive taste response in mice. This suggests that GDF15 may induce an aversion to certain foods in order to correct nutritional stress.
GD15 production is not affected by moderate caloric surpluses or deficits but acts to rectify sustained nutritional stress. GDS15 induces a stress response and creates an aversion for foods containing the nutrients in excess in order to regain nutritional balance.
Contact Bruker for more information.
Patel S, et al. GDF15 Provides an Endocrine Signal of Nutritional Stress in Mice and Humans. Cell Metabolism 2019;29(3):707‑718. https://doi.org/10.1016/j.cmet.2018.12.016